Seeing Melanoma Through a Multispectral Lens

The Cost of Cancer

Of the 132,000 new melanoma patients diagnosed globally each year, approximately 8 or 9% are metastatic when diagnosed, meaning that the disease has progressed to a point where it is very aggressive and nearly impossible to treat. Equally alarming is that melanoma is increasing at a far faster rate than any other form of cancer. In the U.S. alone, melanoma will claim over 10,000 lives this year. Next year that number will likely be higher. 1

Now there is real basis for optimism. Immunotherapies, which are being fast tracked through the approval process because of extraordinary results in early trials, are now moving to first line treatment for the most aggressive and untreatable metastatic cancers, including metastatic melanoma. Although a strategy that leverages one’s own immune system seems obvious, scientists were not able to come up with a therapy that has acceptable side effects until just a few years ago. Recent breakthroughs are leading to truly remarkable results with tolerable side effects, including what appears to be in some cases complete cures. 2

Behind the headlines, however, is another story to tell. Immunotherapy can cost upwards of $150,000 per year for one course of treatment against advanced melanoma. 3 Some patients need multiple treatments to combat the disease. Recent studies also show that while 50% or more of melanoma patients experience remarkable results from such treatments as Adoptive T-cell Therapy (ACT), at least one in three patients are unable to generate those all-important tumor-infiltrating lymphocytes (“TILs”) or T cells that are needed to fight the disease. Instead, they lose precious time and small fortunes in the desperate struggle to save their lives. 4

Defining the Problem

Research Scientists at the Providence Cancer Center in Portland, Oregon, know all about those desperate struggles. As pioneers in immunotherapy, Providence researchers have made huge advances in understanding of how TILs can be cultured and expanded in vitro to potentially help patients suffering from all types of cancer.

“We are translating the latest technology and moving it out of the laboratory,” says Dr. Bernard A. Fox, Chief of the Molecular and Tumor Immunology Laboratory at Providence.

The challenge today is that apparently ACT is stalled in some cases by specific cell-to-cell interactions occurring at the tumor site. To understand the local biology, scientists need to see and quantitatively assess the different types of immune cells infiltrating a tumor and observe the interactions between these immune cells and cancer cells. With a capability to do this, doctors might be able to identify the third to half of cases that will not respond to Adoptive T-cell Therapy and avoid costly and time-consuming approaches that will have no benefit. 5

Making History

Working with PerkinElmer, Dr. Fox and six of his Providence colleagues employed a PerkinElmer Vectra® 3 imaging platform, including inForm® Cell Analysis™ and TIBCO Spotfire® visualization software, to examine the tumor microenvironment of melanoma. Leveraging the Vectra® 3 platform’s multispectral capabilities, the researchers were able to observe and analyze for the first time multiple prognostic markers on a single microscopic tumor sample preserved in paraffin. Prognostic biomarkers correlate with the natural progression or aggressiveness of a disease. So what Fox and company saw, thanks to the Vectra® 3 platform, were a number of historic firsts. Among them was visual confirmation that the presence of CD8+ T cells alone was insufficient to generate a TIL culture –a critical initial step in the success of cancer immunotherapy.

The team also discovered that blocking a protein called CSF-1R, which recruits tumor-infiltrating myeloid cells (TIMs) to suppress tumor immunity, enhances the creation of cancer-killing CD8+ T cells. That finding was deemed so significant it prompted a further evaluation of the anti-CSF-IR strategy, and it has already shown limited results.

Equally important, Fox and his associates may have found a way to increase the success rate of TIL generation in cancer patients who previously failed to do so. “That holds the promise of expanding the use of Adoptive T-cell Therapy to a greater number of patients with melanoma and potentially other malignancies,” Dr. Fox explains.

“Using the Vectra® 3 platform’s seven-color multispectral immunohistochemistry, our team was able to examine the immune environment of tumors in patients with melanoma for the first time,” Dr. Fox says. “While the application of this methodology is at an early stage of research, we consider its greatest promise will be as a means to identify resistance mechanisms at the tumor site. In this era of combination immunotherapy, this information gleaned from the research may be a useful guide to tailor specific therapies to cancer.”

PerkinElmer’s products included in this article are for Research Use Only. Not for use in diagnostic procedures.

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